M. Suzanne Stratton

Phase 3 clinical trial investigating the effect of selenium supplementation in men at high‐risk for prostate cancer

This study was conducted to investigate the effect of Se supplementation on prostate cancer incidence in men at high risk for prostate cancer.

A topical lipophilic niacin derivative increases NAD, epidermal differentiation and barrier function in photodamaged skin

Abstract:  The effects of myristyl nicotinate (MN), a nicotinic acid derivative designed to deliver nicotinic acid to skin without vasodilatation, on subjects with photodamaged skin have been studied. MN increased skin cell nicotinamide adenine dinucleotide (NAD) by 25% (P = 0.001) demonstrating effective delivery of nicotinic acid to skin. Relative to placebo, MN treatment of photodamaged facial skin increased stratum corneum thickness by approximately 70% (P = 0.0001) and increased epidermal thickness by approximately 20% (P = 0.001). In two separate studies, MN treatment increased rates of epidermal renewal by 6% (P = 0.003) to 11% (P = 0.001) and increased the minimal erythemal dose by 8.9 (P = 0.07) and 10% (P = 0.05) relative to placebo. MN treatment resulted in reductions in the rates of transepidermal water loss (TEWL) of approximately 20% relative to placebo on cheeks (P = 0.012) and arms (P = 0.017) of study subjects. Results of a tape stripping challenge before and after MN treatment demonstrated a significant correlation (P = 0.03) between increased skin NAD content and resistance to changes in TEWL for MN treated but not placebo subjects. Rates of TEWL changed more rapidly and to a greater extent in atopic subjects compared with normal subjects. The results indicate that MN enhances epidermal differentiation and barrier function in skin, suggesting that this method of nicotinic acid delivery may prove useful in limiting progression of actinic skin damage and possibly in treating other conditions involving skin barrier impairment.

Oral Selenium Supplementation Has No Effect on Prostate- Specific Antigen Velocity in Men Undergoing Active Surveillance for Localized Prostate Cancer

The Nutritional Prevention of Cancer trial showed a 52% lower incidence of prostate cancer in men supplemented with selenium. As a result, our study was designed to assess whether selenium supplementation attenuates the progression of prostate cancer. A phase 2 randomized, double-blind, placebo-controlled clinical trial was conducted in men with localized nonmetastatic prostate cancer who had elected to forgo active treatment and be followed by active surveillance. A total of 140 men were randomized to placebo (n = 46), 200 μg/d (n = 47), or 800 μg/d (n = 47) selenium p.o. (as selenized yeast) and followed every 3 months for up to 5 years. Prostate-specific antigen (PSA) velocity was used as a marker of prostate cancer progression and was estimated using mixed-effects regression. Adjusting for age, body mass index, baseline selenium, smoking, baseline PSA, race, PSA method, and Gleason score, PSA velocities for the 200 μg/d and 800 μg/d treatment groups were not statistically significantly different from placebo (P = 0.32 and P = 0.61, respectively). In the highest quartile of baseline selenium, men supplemented with 800 μg selenium showed statistically significantly higher PSA velocity as compared with placebo (P = 0.018). Selenium supplementation did not show a protective effect on PSA velocity in subjects with localized prostate cancer. On the contrary, supplementation with high-dose selenium was observed to be a risk factor for increased PSA velocity in men with high baseline plasma selenium concentrations. Cancer Prev Res; 3(8); 1035–43. ©2010 AACR.

Effect of aspirin, other NSAIDs, and statins on PSA and PSA velocity.

Aspirin, other non‐steroidal anti‐inflammatory drugs (NSAIDs), and statins have been associated with lower risk of prostate cancer and its progression, though results have been inconsistent.

Mechanism of action of a dominant negative c-jun mutant in inhibiting activator protein-1 activation

The dominant negative c‐jun TAM‐67 has been shown to inhibit tumor promotion induced by 12‐O‐tetradecanoylphorbol‐13‐acetate and okadaic acid (OA). To better understand this phenomenon, we investigated the mechanism of action of TAM‐67 in response to OA. To identify the mechanism of action, we used a 6xHis‐tagged TAM‐67 as well as chimeric constructs of TAM‐67 that either cannot bind DNA or cannot heterodimerize with wild‐type transcription factors. The results of these studies indicated that TAM‐67 acts by blocking or squelching. The results of elecrophoretic mobility‐shift assays showed that TAM‐67 must act by squelching in response to OA, as TAM‐67 cannot be found in DNA‐binding complexes. We then identified some of the proteins with which TAM‐67 interacts. They include all members of the jun and fos families as well as the cAMP response element binding protein, activating transcription factor‐1, activating transcription factor‐2, and RelA (p65). Thus, we have shown that TAM‐67 squelches the induction of activating transcription factor‐1 transactivation in response to OA and that TAM‐67 is capable of interacting with proteins that control transactivation by binding to the 12‐O‐tetradecanoylphorbol‐13‐acetate response element, cAMP response element and nuclear factor‐κB sites.

Association of Obesity and Smoking With PSA and PSA Velocity in Men With Prostate Cancer

Significant number of prostate tumors are slow growing and could probably be left untreated. However, many are aggressive and can spread rapidly causing patient suffering and/or death. Current technology does not allow physicians to differentiate between slow growing and aggressive tumors at diagnosis. Hence, many patients are exposed to invasive treatment and its associated morbidities such as incontinence and impotence. Markers that enable differentiation between slow and fast progressing cancer will allow physicians to prevent unnecessary treatments on men who may not need them, and focus on the men with aggressive disease. A longitudinal study was conducted (N = 140) using mixed effects regression models to determine the association of obesity and smoking toward prostate cancer progression. These models account for correlation because of repeated measures over time, thus, using maximum amount of information provided by the subject. Estimates thus obtained are more robust and reliable than those obtained using data from a single time point. Rate of change of prostate-specific antigen (PSA) over time (PSA velocity) was used as a measure of prostate cancer progression. Results indicate that PSA velocity of overweight and obese subjects (0.59 and 1.05 ng/mL/year) was not significantly different as compared with normal weight subjects (p values .91 and .31, respectively). For men in the highest tertile of pack-years of smoking, PSA velocity was significantly higher as compared with never smokers 1.57 ng/mL/year ( p = .04). Further studies with larger sample sizes and study designs specific to above exposures are needed before recommendations can be made to reduce weight or reduce/quit smoking.

Strategies in Skin Cancer Chemoprevention

Formal studies of skin cancer began more than 200 yr ago. The first skin tumor model to appear in the literature was reported by London surgeon Percivall Pott in 1775 (1). His account of scrotal cancer in chimney sweeps is considered the historical beginning of cancer research, as he delved beyond treatment into the etiology of the disease (2). Pott’s discovery of the linkage between scrotal carcinoma and soot exposure was the first evidence of a cancer cause, and launched research leading to the discovery of chemical carcinogens and their mechanisms of action.

Treatment of Carcinogenesis

During the past several decades, cancer research has primarily focused on development of cytotoxic agents for treatments. These efforts have significantly improved the prognosis of some types of malignancies including some leukemias, lymphomas, and testicular carcinoma. However, other tumors including metastatic colorectal, breast, and lung carcinomas are still associated with poor prognosis. Innovative approaches to understanding the cellular and molecular mechanisms of the process of carcinogenesis have provided new insights into the paradigm of cancer treatment by exploring the possibilities of early detection, chemoprevention, and treatment of premalignant disease.